In general, our purpose is to pursue investigations to elucidate and evaluate factors responsible for variations in responses of humans to drugs. The factors to be studied will include: 1. environment exposure to chemical agents and drugs; 2. inherent factors such as disease states, hormonal variations, immunologic and genetic status. These studies will be performed at the clinical level utilizing animals to help explain phenomenon seen in humans as well as to suggest possible approaches for such studies in humans. In addition to utilizing existing methods, efforts will be directed toward developing methods to quantitate drug action, absorption, distribution and metabolism in the intact human. We will also expend considerable effort toward evaluating correlations between blood levels of drugs (and/or their metabolites) and their pharmacological actions. The information obtained from these studies should allow drugs to be used therapeutically on a more rational basis.